LMP1 CAR-T for Patients With LMP1 Positive Infectious Diseases and Hematological Malignancies

Clinical Trial for the Safety and Efficacy of Sequential of LMP1 CAR-T for Patients With LMP1 Positive Infectious Diseases and Hematological Malignancies

A study of LMP1 CAR-T for patients with LMP1 positive infectious diseases and hematological malignancies

Study Overview

• Status: Not yet recruiting
• Conditions: Infectious Diseases; Hematological Malignancies
• Intervention / Treatment: Drug: LMP1 CAR T-cells

Detailed Description

This is a single arm, open-label, single-center study. This study is indicated for LMP1 positive infectious diseases and hematological malignancies. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 144 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital，College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Only applicable to the inclusion criteria of CAEBV

1. Subjects who are diagnosed with CAEBV according to the Okano revised standard proposed by the Japanese Ministry of Health, Labour and Welfare Research Group for the Prevention of Refractory Diseases;

2. All CAEBV patients who have not achieved complete remission, including:

   1. Active phase: EBV-DNA level in PBMC is higher than 1×10^2.5 copies/μg DNA, with symptoms and signs of active diseases such as fever, hepatomegaly, splenomegaly, abnormal liver function, decrease of blood three lines, lymphadenopathy, and progressive skin lesions with increased EBV titer in peripheral blood;
   2. inactive phase: EBV-DNA level in PBMC is higher than 1×10^2.5 copies/μg DNA, without symptoms and signs of active diseases;
3. The disease has not yet progressed to hematopoietic lymphohistiocytosis (HLH);

Only applicable to the inclusion criteria of LMP1-positive ENKTL:

1. According to the 2016 WHO classification criteria for lymphocytic tumors: Subjects diagnosed by histopathology as extranodal NK/T cell lymphoma, nasal type (ENKTL) with LMP1 positive in tumor tissue;

2. R/R ENKTL (meets one of the following prerequisites)

   1. Without remission or with progression after receiving second-line or higher-line chemotherapy/chemotherapy + radiotherapy;
   2. Primary drug resistance;
   3. With recurrence after receiving autologous/allogeneic hematopoietic stem cell transplantation;
3. According to 2014 Lugano standard, there should be at least one evaluable tumor lesion.

Only applicable to the inclusion criteria for LMP1-positive HL:

1. According to the 2016 WHO classification criteria for lymphocytic tumors, subjects with Hodgkin lymphoma diagnosed by histopathology (HD) and LMP1 positive in tumor tissue;

2. R/R HD (meets one of the following prerequisites):

   1. Without remission or with progression after receiving second-line or higher-line chemotherapy;
   2. Primary resistance Drugs;
   3. With recurrence after receiving autologous hematopoietic stem cell transplantation;
3. According to the Lugano 2014 standard, there should be at least one evaluable tumor lesion;

Only applicable to the inclusion criteria for LMP1-positive PTLD:

1. Only PTLD after hematopoietic stem cell transplantation;
2. According to the 2016 WHO classification criteria for lymphocytic tumors, subjects with PTLD diagnosed by histopathology and LMP1 positive in tumor tissue;
3. Excluding PTLD of early-stage

4. R/R PTLD (meets one of the following prerequisites):

   1. Without remission or with progression after receiving rituximab-based standard treatment;
   2. Primary drug resistance;
5. According to the Lugano 2014 standard, there should be at least one evaluable tumor lesion

Exclusion Criteria:

Subjects with any of the following exclusion criteria were not eligible for this trial:

1. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
7. Previously treated with any CAR-T cell product or other genetically modified T cell therapies;
8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk ofpatients or interfere with the results of study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration of LMP1 CAR T-cells; Each subject receive LMP1 CAR T-cells by intravenous infusion	Drug: LMP1 CAR T-cells; Each subject receive LMP1 CAR T-cells by intravenous infusion; Other Names: LMP1 CAR-T cells injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Baseline up to 28 days after LMP1 targeted CAR T-cells infusion
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after LMP1 targeted CAR T-cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Activities of Daily Living (ADL) score	Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Instrumental Activities of Daily Living (IADL) score	Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Hospital Anxiety and Depression Scale (HADS) score	Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12
Chronic active EB virus infection (CAEBV), Overall response rate (ORR)	Assessment of ORR (ORR = CR + PR) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
CAEBV，Duration of remission（DOR）	From the first remission after LMP1 CAR-T cells to relapse, death or the last visit	Up to 2 years after LMP1 CAR-T cells infusion
CAEBV, Overall survival (OS)	From the first infusion of LMP1 CAR-T cells to death or the last visit	Up to 2 years after LMP1 CAR-T cells infusion
CAEBV, Relapse rate(RR)	From the first remission after LMP1 CAR-T cells to relapse or the last visit	At Month 6, 12, 18 and 24
CAEBV, Event-free survival (EFS)	From the first infusion of LMP1 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit	Up to 2 years after LMP1 CAR-T cells infusion
Hodgkin's lymphoma(HL), Extranodal NK/T cell lymphoma(ENKTL),Nasal type, Lymphoproliferative disease after hematopoietic stem cell transplantation, (post-HSCT PTLD),Overall response rate (ORR)	Assessment of ORR (ORR = CR + PR) at Month 1, 3, 6, 12, 18 and 24	At Month 1, 3, 6, 12, 18 and 24
HL, ENKTL, PTLD, OS	From the first infusion of LMP1 CAR-T cells to death or the last visit	Up to 2 years after LMP1 CAR-T cells infusion
HL, ENKTL, PTLD, EFS	From the first infusion of LMP1 CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit	Up to 2 years after LMP3 CAR-T cells infusion
Quality of life	Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12	At Baseline, Month 1, 3, 6, 9 and 12

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2021
• Primary Completion (Anticipated): January 15, 2024
• Study Completion (Anticipated): January 15, 2027

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: December 5, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 5, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: CAR T-cell therapy; Infectious diseases; Hematological Malignancies; LMP1
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Disease Attributes; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Infections; Communicable Diseases
• Other Study ID Numbers: LMP1-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No